Growth hormone (GH) secretion is pulsatile en all species studied to date. Growth hormone-releasing hormone (GHRH) appears to stimulate GH synthesis and release whereas somatostatin (SRIF) is involved in the inhibition of GH release. Present understanding of the stimulatory and inhibitory interactions between hypothalamic factors has primarily come from in vitro and animal studies. Likewise, the mechanisms of action of several pharmacological agents that are used to clinically assess GH reserve have only been studied in animal models or by inferential human studies. However, because of large interspecies variation in the control of GH secretion, the data obtained in animals may not be applicable to humans. We have recently begun in vivo human studies that are directed at investigating the role of GHRH in GH secretion, using as a tool, a specific antagonist to GHRH, GHRH-Ant. These studies have allowed us to definitively assign an important role to GHRH in the generation of spontaneous GH pulses in humans as well as to determine that the GH responses to L-dopa and arginine are GHRH dependent. We are now extending our preliminary investigations to explore the mechanisms responsible for GH deficiency in the elderly by determining the dose responses of GH to GHRH-Ant. We suggest that GH deficiency in aging is consequent upon GHRH deficiency. If this were the case, the dose-response curve of the GH suppression by GHRH-Ant should be shifted to the left in the elderly population, i.e. lower doses of antagonist would be needed to suppress plasma GH concentrations.